项目名称： 川芎嗪通过miR-106b-5p调控MDM2/P53信号通路逆转肝癌细胞对奥沙利铂多药耐药的机制研究

项目编号： No.81503299

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 滕凤猛

作者单位： 南京中医药大学

项目金额： 18万元

中文摘要： 肝癌的多药耐药是系统性化疗失败的主要原因，本项目拟对川芎嗪通过miR-106b-5p调控MDM2/P53轴逆转肝癌细胞对奥沙利铂多药耐药的机制进行研究，探索肝癌细胞对奥沙利铂耐药的新靶点，为中药的开发和利用提供新的研究思路。体外建立肝癌细胞对奥沙利铂耐药的模型，应用基因芯片技术筛选耐药差异表达基因，探寻肝癌细胞对奥沙利铂耐药的分子机制；为临床寻找逆转肝癌多药耐药的逆转剂提供理论基础。应用miRNA干扰技术在体内高表达/低表达miR-106b-5p；从基因水平-蛋白网络水平面阐明川芎嗪逆转肝癌多药耐药的分子作用机制，为川芎嗪的临床应用奠定理论基础和提供实验依据。建立耐药细胞皮下移植瘤动物模型，评价川芎嗪逆转肝癌多药耐药的疗效以及减少化疗药物副作用的情况；将基础研究与动物实验相结合，为临床新的治疗方案提供理论和实验基础。

中文关键词： 川芎嗪；逆转剂；多药耐药；化疗敏感性；MDM2/P53信号通路

英文摘要： Multidrug resistance of hepatoma cells is the major cause of systemic chemotherapy failure. This study was projected to elucidate whether Tetramethylphyrazine regulates hepatoma cells to oxaliplatin multidrug resistance by miR-106b-5p and MDM2/P53 signaling pathway, which help to reveal new targets for oxaliplatin multidrug resistance and provide a new thinking for the development and utilization of traditional Chinese Medicine. In order to explore the molecular mechanisms of HCC cells to oxaliplatin resistance, we shall establish the model of HCC cells to oxaliplatin resistance in vitro, and screen the drug resistance genes with cDNA microarray. Accordingly, it would be beneficial to providing theoretical basis of multidrug resistance reversal agents in clinic. Then, we shall use miRNA interference technology to regulate miR-106b-5p expression in vivo, to elucidate the molecular mechanisms of Tetramethylphyrazine reversing hepatoma cells to oxaliplatin multidrug resistance from gene and protein level. It makes for formulating new scheme of clinical treatment in HCC chemotherapy. At last, we’ll transplant subcutaneously the drug resistant hepatoma cells in nude mice, to observe the curative effects and side effects of Tetramethylphyrazine in reversing hepatoma cells to oxaliplatin multidrug resistance. The combination of basic research and animal experiment could provide theoretical and experimental foundation for the new treatment regimens in clinical.

英文关键词： Tetramethylphyrazine;Reversal agents;Multidrug resistance;chemosensitivity;MDM2/P53 signaling pathway